The estimated prevalence of cigarette smoking in the HIV-seropositive population is ~ 50%, over double that in the general population. Furthermore, persons infected with HIV appear to be especially susceptible to the adverse effects of cigarette smoking. Of particular relevance to this RFA is convincing evidence that prior to the onset of AIDS-related pulmonary complications, HIV-seropositive individuals are at increased risk of developing accelerated emphysema. This risk appears to be related to an increased susceptibility to cigarette smoke. In light of the aging of the HIV-seropositive population, the high prevalence of cigarette smoking in this group, and it's increased risk of smoking related lung damage, it is possible that chronic obstructive pulmonary disease (COPD) will soon dwarf other HIV-related pulmonary complications in terms of disease burden. With this as a background, the overall objective of the current proposal is to not merely examine the natural history of HIV-related emphysema in the HAART era, but to investigate whether that natural history can be altered. Indeed, while numerous investigators have highlighted the importance of smoking cessation in HIV-seropositive individuals, there is strikingly little research into this area. The current proposal will study the effect of smoking cessation on the course of HIV-associated emphysema from the symptomatic, physiologic and biologic perspective. As such, we will pursue the following specific aims: Specific Aim 1: To develop and evaluate a specialized smoking cessation intervention for the treatment of nicotine dependence in HIV-seropositive smokers. Specific Aim 2: To examine the effects of smoking cessation on the course of lung function decline, the prevalence of respiratory symptoms and the occurrence/progression of emphysema in a cohort of HIV- seropositive individuals. Specific Aim 3: To explore the effects of smoking cessation on the biology of alveolar macrophages obtained from HIV-seropositive individuals. This proposal is highly significant. To begin with, it will shed insight into the natural history of emphysema in a very susceptible population, advancing our understanding of HIV-related pulmonary complications and the emphysema process in general. More importantly, the proposal will begin to address the efficacy of a smoking cessation regimen in a patient population with an extremely high smoking prevalence. As such, the results obtained herein will have important and immediate clinical relevance.